1. Field of the Invention
This invention is directed to novel compositions for embolizing blood vessels which are particularly suited for treating aneurysms, arteriovenous malformations (AVMs) at high flow fistulas and embolizing blood vessels.
In one embodiment, the compositions of this invention comprise a biocompatible polymer, a biocompatible solvent and a biocompatible contrast agent wherein the viscosity of the composition is at least about 150 cSt and preferably at least about 200 cSt at 40° C.
References
The following publications are cited in this application as superscript numbers:    1 Mandai, et al., “Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer”, J. Neurosurg., 77:497-500 (1992)    2 Kinugasa, et al., “Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer”, J. Neurosurg., 77:501-507 (1992)    3 Casarett and Doull's Toxicology, Amdur et al., Editors, Pergamon Press, New York, pp. 661-664 (1975)    4 Greff, et al., U.S. Pat. No. 5,667,767 for “Novel Compositions for Use in Embolizing Blood Vessels”, issued on Sep. 16, 1997    5 Greff, et al., U.S. Pat. No. 5,580,568 for “Cellulose Diacetate Compositions for Use in Embolizing Blood Vessels”, issued on Dec. 3, 1996    6 Kinugasa, et al., “Early Treatment of Subarachnoid Hemorrhage After Preventing Rerupture of an Aneurysm”, J. Neurosurg., 83:34-41 (1995)    7 Kinugasa, et al., “Prophylactic Thrombosis to Prevent New Bleeding and to Delay Aneurysm Surgery”, Neurosurg, 36:661 (1995)    8 Taki, et al., “Selection and Combination of Various Endovascular Techniques in the Treatment of Giant Aneurysms”, J. Neurosurg, 77:37-42 (1992)    9 Evans, et al., U.S. patent application Ser. No. 08/655,822 for “Novel Compositions for Use in Embolizing Blood Vessels”, filed May 31, 1996.    10 Dunn, et al., U.S. Pat. No. 4,938,763 for “Biodegradable In-Situ Forming Implants and Methods of Producing Same”, issued Jul. 3, 1990
All of the above references are herein incorporated by reference in their entirety to the same extent as if each individual reference was specifically and individually indicated to be incorporated herein by reference in its entirety.
2. State of the Art
Embolization of blood vessels is conducted for a variety of purposes including the treatment of tumors, the treatment of lesions such as aneurysms, uncontrolled bleeding and the like.
Embolization of blood vessels is preferably accomplished via catheter techniques which permit the selective placement of the catheter at the vascular site to be embolized. In this regard, recent advancements in catheter technology as well as in angiography now permit neuroendovascular intervention including the treatment of otherwise inoperable lesions. Specifically, development of microcatheters and guide wires capable of providing access to vessels as small as 1 mm in diameter allows for the endovascular treatment of many lesions.
Embolizing compositions (embolic compositions) heretofore disclosed in the art include those comprising a biocompatible polymer, a biocompatible solvent and a contrast agent which allowed visualization of the in vivo delivery of the composition via fluoroscopy.1-8 Such compositions typically contain no more than about 8 weight percent of biocompatible polymer based on the weight of the total composition.
Notwithstanding the benefits associated with the use of such embolic compositions in treating aneurysms and other vascular disorders, in vivo these compositions formed coherent masses which often suffer from solidification and formation of a coherent mass distal from the point of ejection from the catheter. That is to say that upon ejection of the embolic composition in a vascular site, the coherent mass subsequently formed was often distal and not proximate the ejection port of the catheter. Moreover, upon solidification, the solid mass formed was often linear in shape (i.e., having a “string shape”).
In many circumstances, a contiguous or ball shape precipitate formed at the ejection port is desired (e.g., to fill an aneurysm). Distal solidification of a string shape precipitate makes site specific delivery of the solid mass in the vasculature difficult. As is apparent, site specific delivery of the solid mass is essential for treatment of vascular disorders such as aneurysms. Solidification at points distal to the ejection port, as is common in string shape precipitates, can result in the solid mass forming not in the aneurysm sac but in the artery attendant the aneurysm. Such a string shape precipitate is more prone to fragmentation which can lead to embolization of this artery and possible incapacitation or death of the patient. Moreover, such fragmentation can lead to particles or fragments being “washed” downstream and lodging at undesired locations in the vasculature.
This invention is based, in part, on the discovery that the formation of a solid non-migratory mass having a substantially contiguous or “ball” shape can be achieved by use of embolic compositions comprising a biocompatible polymer, a biocompatible solvent and optionally a contrast agent wherein the composition has a viscosity of at least about 150 cSt at 40° C. The use of such high viscosity embolic compositions was heretofore not preferred in view of the fact that the viscosity of these compositions is significantly higher than those containing 8 weight percent polymer thereby rendering it difficult to employ conventional delivery means (e.g., syringe) for use in combination with the catheter for the controlled delivery of these compositions in vivo.
However, delivery means such as the threaded syringes described, for example, in U.S. Provisional Patent Application Ser. Nos. 60/135,289 and 60/135,287, entitled “THREADED SYRINGE” and entitled “SCREW SYRINGE WITH FORCE RELEASE MECHANISM”, both of which were filed on May 21, 1999, now renders the use of these highly viscous compositions practical. Both of these applications are incorporated herein by reference in their entirety.